Molecular Origin of the Distinct Tabletability of Loratadine and Desloratadine: Role of the Bonding Area - Bonding Strength Interplay.

Purpose: To explain the different tabletability of two structurally similar H1-receptor antihistamine drugs, loratadine (LOR) and desloratadine (DES), based on the molecular basis of bonding area and bonding strength.

Methods: LOR and DES were characterized by powder X-ray diffractometry, thermal analysis, and dynamic water sorption. The compressibility, tabletability, compactibility, and Heckel analysis of their bulk powders and formulations were evaluated.

Highly sensitive detection of Pb and Cu based on ZIF-67/MWCNT/Nafion-modified glassy carbon electrode.

A series of different facile modification layers (MLs) was designed to gradually increase the electrochemical sensing performance of glassy carbon electrode (GCE) for simultaneously detecting Pb and Cu. ML designs were mainly a different combination of ZIF-67, MWCNT and Nafion, and their different electrochemical sensing performances were investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), square wave stripping voltammetry (SWSV) and chronocoulometry. The fabricated sensor, which modified with ZIF-67/MWCNT and Nafion layer, exhibited the biggest response peak current to Pb and Cu.

[Effects of soil permeability improvement and purification of pollutants in urban green space under different matrix composition amendments].

Green land is important carrier in cities. We investigated the effects of soil permeability improvement and purification of pollutants under different matrix composition amendments in Xixian New Area, Shaanxi Province. Six materials, including biochar, vermiculite, perlite, compost, polyacrylamide (PAM) and coir, were mixed with basic materials that were composed of soil and sand (volume ratio of 4:4), and then incubated for 30 days.

Analysis of risk factors for progressive fibrovascular proliferation in proliferative diabetic retinopathy.

Purpose: To investigate the risk factors associated with progressive fibrovascular proliferation (FVP) in proliferative diabetic retinopathy (PDR).

Methods: We retrospectively reviewed the clinical data of patients who underwent pars plana vitrectomy for PDR between August 2017 and October 2019 at our department of ophthalmology. The FVP was divided into five grades based on the coverage area of proliferative membrane.

Propensity score-integrated composite likelihood approach for augmenting the control arm of a randomized controlled trial by incorporating real-world data.

In this paper, a propensity score-integrated composite likelihood (PSCL) approach is developed for cases in which the control arm of a two-arm randomized controlled trial (RCT) (treated vs control) is augmented with patients from real-world data (RWD) containing both clinical outcomes and covariates at the patient-level. RWD patients who were treated with the same therapy as the control arm of the RCT are considered for the augmentation. The PSCL approach first estimates the propensity score for every patient as the probability of the patient being in the RCT rather than the RWD, and then stratifies all patients into strata based on the estimated propensity scores.

Multiple Bioinformatics Analyses of Integrated Gene Expression Profiling Data and Verification of Hub Genes Associated with Diabetic Retinopathy.

BACKGROUND Diabetic retinopathy (DR) is a serious complication of diabetes that can lead to blindness. This study aimed to identify the core genes and molecular functions involved in DR through multiple bioinformatics analyses. MATERIAL AND METHODS The mRNA gene profiles of human DR tissues from the GSE60436 and GSE53257 datasets were assessed with R software and integrated to identify the co-expressed differentially expressed genes (DEGs).

Evidence for immortality and autonomy in animal cancer models is often not provided, which causes confusion on key issues of cancer biology.

Modern research into carcinogenesis has undergone three phases. Surgeons and pathologists started the first phase roughly 250 years ago, establishing morphological traits of tumors for pathologic diagnosis, and setting immortality and autonomy as indispensable criteria for neoplasms. A century ago, medical doctors, biologists and chemists started to enhance "experimental cancer research" by establishing many animal models of chemical-induced carcinogenesis for studies of cellular mechanisms.

Metalloimmunology: The metal ion-controlled immunity.

Metals are essential components in all forms of life required for the function of nearly half of all enzymes and are critically involved in virtually all fundamental biological processes. Especially, the transition metals iron (Fe), zinc (Zn), manganese (Mn), nickel (Ni), copper (Cu) and cobalt (Co) are crucial micronutrients known to play vital roles in metabolism as well due to their unique redox properties. Metals carry out three major functions within metalloproteins: to provide structural support, to serve as enzymatic cofactors, and to mediate electron transportation.

Design of Red Emissive Carbon Dots: Robust Performance for Analytical Applications in Pesticide Monitoring.

Synthesis of red emissive carbon dots (CDs) is highly desirable for sensing applications, as they still remain as bottlenecks in terms of precursor synthesis and product purification. Herein, we have designed a new strategy for realizing efficient red emissive CD optimal emission at 610 nm (fluorescence quantum yield ca. 24.

Simultaneous taste-masking and oral bioavailability enhancement of Ligustrazine by forming sweet salts.

Ligustrazine (or Tetramethylpyrazine, TMP) is an active pharmaceutical ingredient that faces the challenges of bitter taste and low oral bioavailability by the commercial phosphate salt (TMP-Pho). We tackled these challenges by forming salts with two sweeteners, acesulfame (Acs) and saccharine (Sac). Both salts effectively masked the bitter taste of TMP.

Hydrogenolysis of biomass-derived sorbitol over La-promoted Ni/ZrO catalysts.

Ni/LaO/ZrO catalysts were prepared by a step-by-step impregnation method through regulation of the contents of the active component and alkali. The introduction of an alkaline promoter not only enhanced the alkalinity of the catalyst but also improved the dispersion of Ni on the catalyst owing to the strong interaction between Ni and alkali promoter. The synergistic effect between Ni and LaO was beneficial to selective hydrogenolysis of sorbitol.

Structure-function analyses of candidate small molecule RPN13 inhibitors with antitumor properties.

We sought to design ubiquitin-proteasome system inhibitors active against solid cancers by targeting ubiquitin receptor RPN13 within the proteasome's 19S regulatory particle. The prototypic bis-benzylidine piperidone-based inhibitor RA190 is a michael acceptor that adducts Cysteine 88 of RPN13. In probing the pharmacophore, we showed the benefit of the central nitrogen-bearing piperidone ring moiety compared to a cyclohexanone, the importance of the span of the aromatic wings from the central enone-piperidone ring, the contribution of both wings, and that substituents with stronger electron withdrawing groups were more cytotoxic.

Morphologic and histopathologic change of sodium iodate-induced retinal degeneration in adult rats.

Adult teleost fish are capable of regenerating their retinas following injury. In contrast, the adult mammalian retina has little capacity for regeneration. Here, we describe the morphologic and histopathologic course of sodium iodate (NaIO) injection on rat retinas.

About three-fourths of mouse proteins unexpectedly appear at a low position of SDS-PAGE, often as additional isoforms, questioning whether all protein isoforms have been eliminated in gene-knockout cells or organisms.

Most genes in evolutionarily complex genomes are expressed to multiple protein isoforms, but there is not yet any simple high-throughput approach to identify these isoforms. Using an oversimplified top-down LC-MS/MS strategy, we detected, around the 26-kD position of SDS-PAGE, proteins produced from 782 genes in a Cdk4-/- mouse embryonic fibroblast cell line. Interestingly, only 213 (27.

Cervical cancer outcome by type of health care facilities: National Cancer Database, 2004-2015.

The National Cancer Database from 2004 to 2015 was analyzed to identify cervical cancer outcomes associated with demographic and clinical characteristics measured by types of facility. Chi-Square tests were used to compare proportions and logistic regression to determine factors associated with cervical cancer outcomes. Women treated at Academic/Research Programs (ARPs) were younger at diagnosis, more likely black, less educated and more in Stage 2, lived further away from treatment facilities, had less comorbidities and better 5-year survival, and were more likely to be alive at 30 and 90 days after surgery compared to other programs.

Crystallographic and Energetic Insights into Reduced Dissolution and Physical Stability of a Drug-Surfactant Salt: The Case of Norfloxacin Lauryl Sulfate.

A commonly used pharmaceutical surfactant, sodium lauryl sulfate (SLS), has been reported to reduce the dissolution rate of drugs due to the formation of a less soluble drug-lauryl sulfate salt. In this study, we provide direct crystallographic evidence of the formation of salt between SLS and norfloxacin (NOR), [NORH][LS]·1.5 HO.

Microstructures and pharmaceutical properties of ferulic acid agglomerates prepared by different spherical crystallization methods.

Spherical agglomerates of an active pharmaceutical ingredient, ferulic acid (FA), were prepared using four different spherical crystallization methods, i.e., quasi-emulsion solvent diffusion (QESD), anti-solvent, pH shift, and the direct method.

Autophagy, lysosome dysfunction and mTOR inhibition in MNU-induced photoreceptor cell damage.

Progressive photoreceptor death is the main cause of retinal degeneration diseases. Determining the underlying mechanism of this process is essential for therapy improvement. Autophagy has long been considered to be involved in neuronal degeneration diseases, and the regulation of autophagy is thought to have potential implications for neurodegenerative disease therapies.

Molecular Interpretation of the Compaction Performance and Mechanical Properties of Caffeine Cocrystals: A Polymorphic Study.

The 1:1 caffeine (CAF) and 3-nitrobenzoic acid (NBA) cocrystal (CAF:NBA) displays polymorphism. Each polymorph shares the same docking synthon that connects individual CAF and NBA molecules within the asymmetric unit; however, the extended intermolecular interactions are significantly different between the two polymorphic modifications. These alternative interaction topologies translate to distinct structural motifs, mechanical properties, and compaction performance.

Propensity score-integrated composite likelihood approach for incorporating real-world evidence in single-arm clinical studies.

In medical product development, there has been an increased interest in utilizing real-world data which have become abundant with recent advances in biomedical science, information technology, and engineering. High-quality real-world data may be analyzed to generate real-world evidence that can be utilized in the regulatory and healthcare decision-making. In this paper, we consider the case in which a single-arm clinical study, viewed as the primary data source, is supplemented with patients from a real-world data source containing both clinical outcome and covariate data at the patient-level.

High-activity Mo, S co-doped carbon quantum dot nanozyme-based cascade colorimetric biosensor for sensitive detection of cholesterol.

Nanozymes have drawn considerable attention because of their lower cost, higher stability and convenient preparation compared to protein enzymes. In the present work, Mo, S co-doped carbon quantum dots (Mo-CQDs) as a peroxidase mimic were used to fabricate a cascade colorimetric biosensor to detect cholesterol. The Mo-CQDs possess a robust peroxidase-like activity, and they can easily catalyze 3,3,5,5-tetramethylbenzidine (TMB) to produce an oxidized TMB in the presence of HO.

Propensity score-integrated power prior approach for incorporating real-world evidence in single-arm clinical studies.

We are now at an amazing time for medical product development in drugs, biological products and medical devices. As a result of dramatic recent advances in biomedical science, information technology and engineering, ``big data'' from health care in the real-world have become available. Although big data may not necessarily be attuned to provide the preponderance of evidence to a clinical study, high-quality real-world data can be transformed into scientific evidence for regulatory and healthcare decision-making using proven analytical methods and techniques, such as propensity score methodology and Bayesian inference.

Selective Preparation of 4-Alkylphenol from Lignin-Derived Phenols and Raw Biomass over Magnetic Co-Fe@N-Doped Carbon Catalysts.

Lignin valorization to produce high-value chemicals selectively is an enormous challenge in biorefinery. In this study, 4-alkylphenol, formed by breaking the robust C -OCH bonds solely with the retention of other structures in lignin-derived methoxylalkylphenols, was produced selectively over a Co -Fe @NC catalyst from real lignin oil as feedstock, which was obtained by a "lignin-first" strategy from either birch or cornstalk. A yield of 64.

Comprehensive Analysis of CRISPR/Cas9-Mediated Mutagenesis in by Genome-wide Sequencing.

The clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein (Cas) system has been widely applied in functional genomics research and plant breeding. In contrast to the off-target studies of mammalian cells, there is little evidence for the common occurrence of off-target sites in plants and a great need exists for accurate detection of editing sites. Here, we summarized the precision of CRISPR/Cas9-mediated mutations for 281 targets and found that there is a preference for single nucleotide deletions/insertions and longer deletions starting from 40 nt upstream or ending at 30 nt downstream of the cleavage site, which suggested the candidate sequences for editing sites detection by whole-genome sequencing (WGS).